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The third son of John Russell, 6th Duke of Bedford, and known as Lord John Russell until 1861, Russell was briefly educated at Westminster School, then educated by tutors because of delicate health. He attended Edinburgh University and travelled in Europe before being elected as Whig M.P. for the borough of Tavistock, controlled by his family, in 1813. He resigned on health grounds in 1817 but was returned again the following year. Other seats held by Russell were Huntingdonshire (1820-1826), Bandon (1826-1830), Tavistock (1831), South Devonshire (1831-1835), Stroud (1835-1841), and the City of London (1841-1861).
From 1819 onwards he was a passionate supporter of parliamentary reform, unsucessfully advocating the redistribution of seats in 1822 and 1826. He introduced a bill for repeal of the Test and Corporation Acts in 1828, was one of the four men who drafted the Great Reform Bill, and was singly responsible for introducing it into Parliament three times in 1831 and 1832, and amending the final version which was finally granted Royal Assent in June 1832.
In 1831 he had entered government as Paymaster-General of the Forces, and soon afterwards became a member of the Cabinet. In 1835 he was appointed by Melbourne as Home Secretary and Leader of the House of Commons. In 1839 he became Colonial Secretary. When Melbourne's government fell in 1841 he became leader of the Opposition, and on Peel's defeat in 1846 became Prime Minister.
During his period in office from 1831 to 1852 he continued the work of social reform by introducing the Municipal Corporations Act, reducing the number of capital offences, removing restrictions placed on the Jews, working for the liberalisation of government and economy in Ireland, and passing the Factory Act and the Public Health Act. However, his government was criticized for failures during the Irish Famine in the late 1840s, and conflict between the Foreign Secretary, Lord Palmerston, in 1851, helped to bring down Russell's administration.
Russell resigned as Prime Minister in 1852 but remained in the Cabinet, briefly as foreign secretary, and from 1853-1855 as a minister without portfolio. In 1855 he spent small amounts of time as plenipotentiary to the Vienna Congress, and Colonial Secretary, but again resigned from office in July of that year. In 1859 he was appointed by Palmerston as Foreign Secretary, supporting the unification of Italy, and he became Prime Minister for a second time on Palmerston's death in 1865. The following year he resigned, and took no further active government posts. However, he continued to attend the House of Lords.
He was ennobled as Earl Russell of Kingston Rissell and Viscount Amberley of Amberley and Ardsalla in 1861. Russell was also a published author, producing essays on history and government, a novel, and a play between 1819 and 1832, an edition of letters of the 4th Duke of Bedford between 1842 and 1846, and a biography of Charles James Fox in 1859.